1 Neurochemical changes and tissue weights were measured following intrastriatal injection of 2.5 microgram of kainic acid in 2 microliter of 0.9% w/v NaCl solution (saline) in the rat. 2 After kainic acid the striatum and neocortex on the injected side showed a progressive reduction in weight, the neocortex showing the greatest absolute weight loss and the striatum the greatest percentage change. 3 Large (80-90%) reduction in choline acetyltransferase (CAT) and L-glutamate decarboxylase (GAD) activities in the striatum occurred within 2-4 days of the injection and persisted at least 10 weeks. At 10 weeks CAT and GAD activities were unaltered in the neocortex. 4 The absolute content of dopamine in the striatum was not different from control 5 days after the injection of kainic acid but was reduced at 2 and 10 weeks. At 2 weeks the concentration (microgram/g wet weight) of dopamine also was reduced but at 10 weeks it was near normal due to atrophy of the striatum. 5 The high affinity glutamate uptake into a crude synaptosomal preparation of the striatum was reduced by 64% 5 days after kainic acid and still reduced by 67% at 10 weeks. 6 The efflux of glutamate from slices of the striatum in the presence of 52 mM K+ was reduced by approximately 75% 5 days and 15 weeks after kainic acid. 7 In vitro kainic acid (10(-4) M) neither altered the high affinity uptake of radiolabelled glutamate into a homogenate of the striatum, nor released endogenous glutamate from slices of striatum.